Whole blood collected from a donor is used for transfusion, as is, only in rare cases, but is commonly separated into components, such as a red cell product, platelet product, plasma product, and the like to be stored for transfusion. Since micro aggregates and leukocytes contained in these blood products cause various side effects after transfusion, these undesirable components are often removed before the blood products are used for transfusion. The need of removing the leukocytes has been widely recognized in recent years, and some European countries legislate the blood products to use for transfusion after applying a treatment for removing leukocyte.
The most common method of removing leukocytes from blood products is by processing blood products using a leukocyte-removing filter. Conventionally, blood products have been processed using a leukocyte-removing filter in many cases at the bedside when blood transfusion is performed. In recent years, however, to improve quality control of leukocyte reduced products and efficiency of leukocyte removal operations, it is more common to process the blood in blood centers before storing the blood products.
A blood collecting and separation set composed of two to four flexible bags, guide tubes for connecting the bags, an anticoagulant, a red cell preservative solution, and blood collecting needles has been used for collecting the blood from a donor, separating the blood into plural blood components, and storing each blood component. A system called a “closed system” or an “integrated system”, in which the leukocyte-removing filter is integrated into the blood collecting-separation set, is widely used as a system that can be favorably used for “prestorage leukocyte reduction”.
Such a system is disclosed in Japanese Patent Application Laid-open No. 01-320064, WO 92/20428, and the like.
While a filter comprising a filter element made of a non-woven fabric or a porous material packaged in a hard housing such as polycarbonate has been widely used for conventional leukocyte removing filters, it has been a problem that a steam sterilization process that is widely used for sterilization of the blood collecting-separation set can be applied to the filter only with difficulty since the housing has low gas permeability. The closed systems include a system in which the leukocytes are first removed from the whole blood product after collecting the blood, followed by removing the leukocyte removing filter to subject the system to centrifugation for separating each component, and a system in which the leukocytes are removed after separating the whole blood into plural blood components by centrifugation. In the latter case, however, the leukocyte-removing filter is subjected to centrifugation together with the blood collecting and separation set. In this instance, a hard may damage bags and tubes, or the housing itself may not withstand the stress and may be damaged during centrifugation.
To solve this problem, flexible leukocyte-removing filters, in which the housing is made of the same or a similar material having superior flexibility and high vapor permeability as used for the bags of the blood collecting -separation set, have been developed.
These filters are broadly classified into the type in which the filter elements are welded to a sheet-like flexible frame, which is then welded to a housing material (European Patent Publication No. 0 526 678, Japanese Patent Application Laid-open No. 11-216179) and the type in which the flexible housing is directly welded to the filter elements (Japanese Patent Application Laid-open No. 7-267871, WO 95/17236). The former type may be hereinafter called the frame welding type and the latter may be called the housing welding type.
When processing blood in these types of leukocyte-removing filters, the bag containing a blood product to be processed, connected to the blood inlet port of the filter via a tube, is placed at a height 20-100 cm higher than the filter to allow the blood product to pass through the filter by gravity. After filtration, the blood product is stored in a recovery bag connected to the blood outlet port of the filter via a tube. During filtration, a pressure loss is caused due to the resistance of the filter element, whereby the pressure in the space on the inlet side of the filter is maintained positive with respect to the atmospheric pressure. In the case of the filter attached to a flexible housing, the flexibility of the housing itself makes the housing swell like a balloon due to the positive pressure, thereby pressing the filter element against the outlet port side housing.
The bag for filling blood processed by the filter is usually placed at a height 50-100 cm lower than the filter. Since the blood flows in the flow channel on the downstream side by gravity, the pressure on the outlet side of the filter tends to become negative. For this reason, the flexible housing tends to adhere to the filter element. Specifically, because the filter element in the filter using a flexible housing tends to be caused to adhere to the housing on the outlet port side due to the double forces, the blood flow is obstructed, resulting in difficulty in ensuring a sufficient flow rate. This has been a longstanding problem.
Various countermeasures for this problem have been proposed in the past. Typical countermeasures include a method of inserting a soft polyvinyl chloride tube called a “connecting rod” between the filter element and outlet port side housing to prevent adhesion (EP 0 526 678), a method of preventing the adhesion by providing irregularities with a depth of 0.2 to 2 mm on the internal surface of the soft housing (Japanese Patent Application Laid-open No. 11-216179), and a method of inserting a screen made of knit fiber (WO 95/17236). However, as described in Japanese Patent Application Laid-open No. 11-216179, the method of inserting a connecting rod or a screen has been considered to have a risk of inducing defective welding of the housing if the other materials are inserted. Another problem of this method is an increase in the production cost due to the complicated process and use of extra materials.
In addition, if a connecting rod is used, the effect of preventing adhesion may be limited to the neighborhood of the connecting rod. Thus, the method of using a connecting rod may not provide a satisfactory effect. The method of providing irregularities on the internal surface of the housing disclosed in Japanese Patent Application Laid-open No.11-216179 has been proposed as a countermeasure for solving the problem in the method of inserting a connecting rod or a screen. When the housing material is directly welded to the filter element, however, the method has a risk of welding failure due to irregularities on the internal surface and may decrease the pressure resistance of the housing. Therefore, the application of this method was limited to the frame welding type filter.
In this manner, conventional technologies to prevent the adhesion of the housing on the outlet port side with the filter element due to negative pressure produced on the outlet side have been based on the means of providing a spacer with a clearance that can function as a flow channel for blood between the housing and the filter. This approach has not necessarily been successful.